One of the major challenges in ethanol research is to identify conserved genetic mechanisms that influence the effects of ethanol on behavior. Integrated molecular studies in mice and humans in conjunction with preliminary genetic analyses in my lab indicate that the Drosophila model is well suited for identifying conserved genes underlying ethanol behavior. In this pilot project we will expand on our preliminary work by exploiting the Drosophila model to evaluate several candidate loci for their impact on locomotor behavior in the presence of ethanol. All of the candidate genes we will investigate are good orthologues of mouse and human genes based on primary amino acid sequence and presence of conserved protein domains. In Aim 1 we will assess the role of multiple candidate genes in ethanol sensitivity. In Aim 2, we will determine whether these candidate genes influence ethanol tolerance. In both Aims, we will explore additional candidate genes that work in concert with loci that influence ethanol sensitivity or tolerance. The planned pilot project is a key step forward in using the Drosophila model to identify conserved genetic mechanisms underlying ethanol behavior.